The prostate is highly prone to malignant disease. In Australia, approximately 20,000 men are diagnosed and over 3,000 die from prostate cancer (PCa) each year . For decades, human PCa cell lines such as LNCaP and PC3 have been used for the pre-clinical evaluation of new cancer therapies. Mostly, these simple two-dimensional (2D) models have been unsuccessful.
Our fundamental hypothesis is that 2D models do not reflect the complexity of PCa or take into account patient variability. Although prostatic tumours are epithelial in origin, it is well established that the prostate microenvironment (stroma, extracellular matrix, vasculature, immune cells and hormones) plays an integral role in tumourigenicity. However, currently most therapies are targeted towards the malignant epithelium, with the stroma and other components often overlooked.
There is an immediate need to develop multicellular 3D in vitro models of PCa to accurately mimic the in vivo architecture of the prostate. Whilst xenograft models provide a valuable platform, these are complex, costly and technically challenging. To this end, we aim to develop a novel 3D bioengineered in vitro model that can incorporate multiple cell types for the study of PCa.
Poly (ε-caprolactone) (PCL) scaffolds were fabricated using direct writing by way of melt electrospinning. PCL filaments were spun in a 0/90⁰ pattern at a distance of ~100µm to allow for cellular infiltration. Primary prostate fibroblasts were successfully incorporated onto the scaffold and were shown to proliferate and deposit extracellular matrix to form a stromal network. Importantly, this stromal network could instruct the morphology of a prostate epithelial cell line when incorporated into the 3D microenvironment.
In summary, the development of accurate and reproducible 3D bioengineered PCa constructs, which support relevant primary human cells with a 3D arrangement, will provide the field with more realistic alternatives to both in vitro and animal models being used today.